The objective of the proposed research is to gain further nutritional and biochemical knowledge about the propionogenic potential of polyunsaturated fats. Substitution of a basal diet containing 10 to 20% saturated and monounsaturated (the usual human dietary composition) with polyunsaturated fats produces an antiketogenic and antiglycolytic response and increases the requirement for vitamin B12 and biotin. We have presented data in support of a gamma-oxidative pathway by which propionate could be produced from linoleate. However, in vitro proof that gamma-oxidation of linoleate is responsible for the propionogenicity of polyunsaturated fats is lacking. The proposed research will center on determining the in vitro cofactors required to demonstrate gamma-oxidation of linoleate. Tissues to be utilized include rat muscle and several autopsy tissues plus fibroblast cultures from methylmalonicacidemic children. The present rationale of diet therapy of the later inborn error in propionate metabolism plus ketotic hyperglycinemia should be significantly improved by present knowledge on the nutritional interaction of B12 and biotin with dietary fat composition. The clinical health and levels of serum and urinary metabolites in these children will be monitored before and after changes in fat composition of the prescribed formulas. If the clinical picture is improved, successful dietary intervention at an earlier age will be more likely with a decreased likelihood of mental retardation and ketoacidosis.